By Pamela Barbaglia and Anjuli Davies

LONDON (Reuters) - U.S. healthcare company Johnson & Johnson has raised its offer for Actelion, a source told Reuters on Tuesday, stepping up pressure on the Swiss biotech firm to accept a takeover deal.

J&J had increased its offer, which has not yet been made public, after nearly two months of informal talks which have so far not resulted in a deal, the source added.

The main stumbling block is that Actelion wants J&J to become a major shareholder in a new entity combining the Swiss group with some of J&J's activities, whereas the U.S. company wants a straightforward takeover, the source said.

Actelion shares closed up 10 percent at 209 Swiss francs, just off a record high, following news of the higher offer.

J&J has become one of the world's biggest healthcare companies through hundreds of acquisitions, in which it has nearly always bought entire companies or drugs outright.

Actelion co-founder and Chief Executive Jean-Paul Clozel has fended off previous attempts to wrest the Swiss firm from him, including a reported takeover approach by Shire last year and an activist campaign in 2011 by U.S. hedge fund Elliott Advisors.

Clozel and his wife Martine, who is Actelion's chief scientific officer, founded the business in 1997. They have been trying to expand its portfolio, which consists of three main drugs focused on treating PAH, a deadly buildup of pressure in blood vessels between the heart and lungs.

Earlier, Bloomberg News reported that Actelion had rejected an offer of 246 francs per share, valuing the Swiss company at around 26.5 billion Swiss francs ($26 billion). The Clozels, both physicians who worked at Roche before setting up Actelion, still own more than 3 percent of its shares.

Recent pharma deals have commanded significant premiums, with Pfizer paying $14 billion for cancer specialist Medivation, double its pre-deal value.

RARE DISEASES

Actelion, whose rare-disease focus makes it an attractive target because its drugs face less price pressure than more widely used medicines, was not available for comment.

A spokesman for Johnson & Johnson declined to comment.

The companies had confirmed last week they were in talks about a possible transaction.

Citigroup is advising J&J, while Bank of America is working with Actelion, two sources said. Both banks declined to comment.

Acquiring the Swiss company would boost J&J's drug pipeline and diversify its prospects. Its biggest product, the arthritis drug Remicade, faces cheaper competition from Pfizer Inc..

Actelion is also growing. Although its blockbuster Tracleer's patent has expired, its new treatment Opsumit's annual sales are set to hit 1.9 billion francs by 2020, according to Reuters data, while just-introduced Uptravi sales could top 2.5 billion francs.

The talks between the two companies began in October, the first source said.

The companies had originally discussed a transaction without a big premium, focusing on some form of share deal or an asset swap, the source said.

John Rountree, director with London-based consultancy Novasecta, said a structured transaction allowing Actelion to benefit from J&J's scale without losing its independence could work for both sides.

One option might be for J&J to mimic Roche, which bought 60 percent of Genentech in 1990, leaving it to operate independently, before acquiring the rest of the biotech in 2009.

(Additional reporting by Ben Hirschler in London, John Miller in Zurich and Ludwig Burger in Frankfurt; Editing by Alexandra Hudson and Alexander Smith)